Salt Treatment Confers Protection Against Acute Carp Edema Virus Reinfection While Promoting Viral Persistence

Carp edema virus (CEV) infects the common carp (Cyprinus carpio) and causes the lethal koi sleepy disease (KSD). Signs of KSD include respiratory, detoxification, and osmoregulatory difficulties. Salt treatment re-equilibrates blood sodium levels and can save the fish. However, it is unclear whether these fish are immunized, remain chronically infected, and shed the virus, which could cause concern for aquaculture and the international fish trade. To address this issue, we examined the physiological and immunological responses following the infection of naturally immunized and naïve fish. Primary CEV infection induces inflammation in the gills and recruits granulocytic leukocyte infiltrates to the lamellae. Immunologically, the antiviral response driven by type I interferon is activated; however, both T and B lymphocytes fail to respond. As part of an immunization strategy, a primary infection followed by salt treatment effectively nullifies the pro-inflammatory response and lymphocyte immunosuppression during CEV reinfection. Our data indicate that immunization enables mechanisms such as lymphocyte activation, differentiation, antigen presentation, and an adaptive immune response and antibody production. However, immunized fish are unable to fully clear the virus for a significant period, during which they are most likely to shed infectious particles.